Hydrophilic pressure sensitive adhesives

ABSTRACT

A hydrophilic, pressure sensitive adhesive of a poly(ethylene oxide) derived network plasticized with an essentially non-volatile, polar plasticizer present in an amount sufficient to form a cohesive, pressure sensitive adhesive. The polymeric network is prepared from an oligomeric precursor comprising difunctional poly(ethylene glycol) moieties which have been end-capped with ethylenically unsaturation. The adhesive is useful as a biomedical adhesive for transmitting or receiving electrical signals as a component of a biomedical electrode. The adhesive is also useful as a drug delivery device to deliver pharmaceuticals or other active ingredients to or through mammalian skin. The adhesive is also useful as a component in a skin covering for protecting mammalian skin or mammalian skin openings with antimicrobial agents. A method of preparation of the adhesive is also disclosed.

This is a division of application No. 07/983,688 filed Dec. 1, 1992 nowU.S. Pat. No. 5,489,624.

FIELD OF THE INVENTION

This invention relates to hydrophilic poly(ethylene oxide) (PEO)pressure sensitive adhesives and medical products using such adhesives.

BACKGROUND OF THE INVENTION

Previously, hydrophilic pressure sensitive adhesives based on PEOpolymer networks have been prepared. Examples of hydrophilic pressuresensitive adhesives based on PEO polymer networks are disclosed in U.S.Pat. No. 4,684,558 (Keusch et al.); U.S. Pat. No. 4,706,680 (Keusch etal.); and U.S. Pat. No. 4,777,954 (Keusch et al.) which teach thepreparation of an adhesive poly(ethylene oxide) hydrogel sheet bysubjecting an aqueous PEO solution to high energy radiation.

Also, European Patent Publication 0 271 292 (Ansell) teaches thepreparation of a skin friendly PSA by reacting a polyfunctionalisocyanate with a polyoxyalkylene diol monoalkyl ether and ahydroxyl-containing ester of (meth)acrylic acid and then crosslinkingthe polymer (optionally in the presence of 40 to 65% water) by means ofirradiation.

Also, U.S. Pat. No. 4,855,077 (Shikinami et al.) and the DerwentAbstract of Japanese Patent Publication 62-139628 (Takiron), teach thepreparation of an ion-conductive polymer adhesive agent by reacting analkylene oxide containing polyol with a polyurethane polyisocyanateprepolymer in the presence of an ionic compound which can include water.

U.S. Pat. Nos. 4,497,914 and 4,650,817 (both Allen et al.) also teachthe reaction of a polyoxyalkylene polyol with an organic polyisocyanatewhile incorporating a hydrophilic filler to give an elastomeric adhesivefor skin contacting applications. The presence of water is specificallyexcluded, presumably to prevent undesirable side reaction with theisocyanate.

U.S. Pat. No. 4,273,135 (Larimore et al.) discloses poly(oxyethylene)(also known as PEO) as one of the non-ionic synthetic hydrophilicpolymers useful as a conductive material for a biomedical electrode andsuggests plasticization with alcohols as a means of impartingconformability.

Methods of preparing difunctional (telechelic) poly(ethylene glycol)swith free-radically polymerizable end groups are known in the art. Forexample, U.S. Pat. No. 3,928,299 (Rosenkranz et al.) and U.S. Pat. No.4,233,425 (Tefertiller et al.) both disclose products resulting fromreaction of poly(alkyleneoxide)s with compounds such as isocyanatoethylmethacrylate. U.S. Pat. No. 3,509,234 (Burlant et al.) discloses areaction of a hydroxylated polymer with first a diisocyanate and then ahydroxyalkyl (meth)acrylate. Also, U.S. Pat. Nos. 4,777,276; 4,837,290;4,914,223; and 4,996,243 (all Rasmussen et al.) disclose reactionproducts obtained from vinyl dimethyl azlactone and poly(ethyleneglycol) diamines.

SUMMARY OF THE INVENTION

The current invention provides a family of hydrophilic pressuresensitive adhesives based on plasticized poly(ethylene oxide) (PEO)derived networks.

"Poly(ethylene oxide) derived networks" or "PEO derived networks" meansnetworks derived from poly(ethylene oxide) or copolymers ofpoly(ethylene oxide) connecting polymer chains formed from ethylenicallyunsaturated moieties.

PEO derived networks are prepared by free-radically polymerizingoligomeric precursors of difunctional (i.e., telechelic) poly(ethyleneglycol) (PEG) which has been end-capped with ethylenically unsaturatedfunctionality.

Hence, the oligomeric precursor used to prepare adhesives of the presentinvention has a low viscosity, is readily processable, and is free ofsolvents that must be removed after polymerization, i.e., solventless.Further, the crosslink density of the precursor is predetermined. Also,the adhesives can be prepared rapidly and reliably without requiringspecialized equipment and without generating concerns about potentiallytoxic or irritating unreacted low molecular weight monomers.

The method of the invention permits great latitude in the choice offormulation used, allowing one to tailor performance attributes over awide range. This latitude for PEO pressure sensitive adhesives waspreviously unavailable in the prior art.

The adhesives of the present invention and their method of preparationsolve problems encountered by the prior art efforts.

None of the references disclosing PEO polymer systems identified aboveteach the use of essentially non-volatile polar plasticizers, such aslow molecular weight poly(ethylene glycol)s, to plasticize PEO polymersformed from oligomeric precursors containing poly(ethylene glycol)moieties, in order to form hydrophilic PEO pressure sensitive adhesives.

Use of such essentially non-volatile polar plasticizers provides a widerlatitude in imparting "feel" and adhesive characteristics to theresulting hydrophilic pressure sensitive adhesive. The essentiallynon-volatile polar plasticizers also serve as a humectant to help retainmoisture under ambient conditions and prevent the resulting hydrophilicPEO pressure sensitive adhesive gel from embrittling due to waterevaporation. Otherwise, a PEO polymer plasticized with essentiallyvolatile plasticizers will have a very short useful life in ambientconditions.

Such essentially non-volatile polar plasticizers cannot be used witholigomeric precursors in the methods taught by Keusch et al. referencedabove because the essentially non-volatile polar plasticizers willseriously reduce the crosslinking efficiency. Also, such essentiallynon-volatile polar plasticizers cannot be used in the Shikinami-Takironor Allen et al. approaches because an isocyanate moiety will not be ableto discriminate between such plasticizers and the polyol meant forreaction.

The present invention is also different from the teaching of Larimore etal. because Larimore et al. teach toward requiring coating and drying toprepare a conformable cohesive film. No curing step is described orcontemplated. Larimore et al. do not therefore teach the in situpreparation of the hydrophilic pressure sensitive adhesives in asolventless fashion using oligomeric precursors in the presence ofessentially non-volatile polar plasticizers.

The references teaching methods of preparing difunctional (telechelic)poly(ethylene glycol)s with free-radically polymerizable end groups donot disclose that useful materials result when these oligomers arepolymerized in the presence of non-reactive diluents such asessentially, non-volatile polar plasticizers.

The hydrophilic pressure sensitive adhesives of the present inventioncomprise a crosslinked, swellable PEO derived network formed by freeradical polymerization of at least one oligomeric precursor of FormulaI:

    X--Y--[(CH.sub.2 CH.sub.2 O).sub.n --R--O--].sub.p --(CH.sub.2 CH.sub.2 O).sub.n --CH.sub.2 CH.sub.2 --Y--X                       I

wherein X are monovalent moieties having ethylenic unsaturation,

Y are organic divalent linking groups which serve to activate X towardsfree radical polymerization,

R is an organic divalent linking group,

n is an integer of about 10 to about 350,

and p is an integer of about 0 to about 30,

such that 45<n(p+1)<450, in the presence of sufficient essentiallynon-volatile polar plasticizer as to render the PEO derived networkpressure sensitive adhesive.

Preferably, the PEO derived network comprises from about 4 to about 60weight percent of the pressure sensitive adhesive and the essentiallynon-volatile polar plasticizer comprises from about 96 to about 40weight percent of the pressure sensitive adhesive in order to render thePEO derived network pressure sensitive adhesive.

The function of n(p+1) being between 45 and 450 is satisfied when thetelechelic polyethylene glycol moiety has a molecular weight rangingfrom about 2,000 to about 20,000.

In a preferred embodiment the essentially non-volatile polar plasticizeris a hydroxy-containing plasticizer selected from the group consistingof monohydric alcohols, polyhydric alcohols, aromatic alcohols, andmixtures of water and such alcohols where the amount of alcohol issufficient to render the plasticizer essentially non-volatile.

Optionally, hydrophilic pressure sensitive adhesives of the presentinvention can also contain an electrolyte. In another aspect of thepresent invention, the ionically conductive, hydrophilic pressuresensitive adhesive can be used as a component in biomedical electrodes.

The process of preparing hydrophilic pressure sensitive adhesives of thepresent invention involves subjecting a mixture of the telechelic PEGoligomeric precursor and essentially non-volatile polar plasticizer to asource of free radicals to induce free radical polymerization of theoligomeric precursor in the presence of plasticizer to form a PEOderived pressure sensitive adhesive.

Non-limiting examples of methods of free radical polymerization includeusing free radicals generated from thermal, redox, or photochemicalinitiators as well as those due to exposure of the mixture to actinicradiation.

A feature of the present invention is the solventless preparation of aPEO derived network plasticized by essentially non-volatile polarplasticizer to form hydrophilic pressure sensitive adhesives.

Another feature of the present invention is the formation of hydrophilicpressure sensitive adhesives having electrolyte therein to render theadhesive ionically conductive.

An advantage of the present invention is the ease of solventless, insitu polymerization of a PEO pressure sensitive adhesive that isresistant to loss of plasticity due the presence of essentiallynon-volatile polar plasticizer.

Non-limiting embodiments of the invention follow a brief description ofthe drawing.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a top plan view of a biomedical electrode containinghydrophilic pressure sensitive adhesive of the present invention.

FIG. 2 is an exploded sectional view of the biomedical electrode of FIG.1.

FIG. 3 is a sectional view of a medical mammalian skin coveringcontaining hydrophilic, pressure sensitive adhesive of the presentinvention.

FIG. 4 is a sectional view of a pharmaceutical delivery devicecontaining hydrophilic, pressure sensitive adhesive of the presentinvention.

FIG. 5 is an exploded view of a biomedical electrode using thehydrophilic, pressure sensitive adhesive of the present invention anddescribed in the Examples.

EMBODIMENTS OF THE INVENTION

Hydrophilic PEO pressure sensitive adhesives of the present inventionare prepared by exposing to a source of free radicals a difunctionaloligomeric precursor containing a poly(ethylene glycol) moiety in thepresence of essentially non-volatile, polar plasticizer compatible withthis polymer in an amount to render the resulting PEO derived network apressure sensitive adhesive.

In order for the resulting swollen PEO derived network to possess adegree of pressure sensitive tack, preferably the oligomeric precursorshould be present in an amount ranging from about 4 to 60 weight percentof the final PEO pressure sensitive adhesive with the balance comprisingessentially non-volatile polar plasticizer.

Insufficient precursor amounts can lead to difficulty duringpolymerization, yielding a polymer network having inadequate cohesivestrength. Excessive precursor can lead to a resulting polymeric networkhaving an excessive modulus, which diminishes adhesive properties.

Similarly, the molecular weight of the telechelic poly(ethylene glycol)in the oligomeric precursor can affect adhesive properties since thattelechelic poly(ethylene glycol) moiety in the polymer determines thecrosslink density of the resulting polymer network. Insufficientmolecular weight results in a brittle, tack free elastomer. Excessivemolecular weight results in diminished cohesive strength.

Preferably, molecular weights (number average) for the telechelicpoly(ethylene glycol) range from about 2,000 to about 20,000 g/mole.Molecular weights in this region polymerize to yield a polymer having anappropriate balance of tack and cohesive strength necessary forproviding a pressure sensitive adhesive after plasticization.

Most preferably, the optimum balance of adhesive properties is obtainedwhen the weight percent of polymer network ranges from about 15 to about25 weight percent and the molecular weight for the telechelicpoly(ethylene glycol) ranges from about 6,000 to about 12,000 g/mole.

Poly(ethylene glycol) homopolymers terminated with either hydroxyl orprimary amine functionality are commercially available within thepreferred molecular weight range and serve as suitable moieties to thedesired oligomeric precursors. Alternatively, lower molecular PEG diolsor diamines can be condensed with coupling agents, for example,diisocyanates (to provide polyurethanes and polyureas) or diacids oresters (to provide polyesters and polyamides) to give moieties to theoligomeric precursors of appropriate molecular weight by proper choiceof reactant ratios.

When such chain extension of low molecular weight PEG diols and diaminesis used to increase molecular weight into the preferred region, thecondensation of the coupling agents with the PEG hydroxyl or aminefunctionality leads to non-poly(ethylene glycol) radicals enchained inthe PEG oligomeric precursor. These non-poly(ethylene glycol) radicalsare represented by the organic divalent linking group R in Formula Iabove.

As one skilled in the art will recognize, when a molar excess of PEGdiol or diamine is used relative to the coupling agent, a highermolecular weight PEG diol or diamine results. On the other hand, whenthe coupling agent is present in excess, the chain extended PEG isterminated with the functionality present in the coupling agent (e.g.,isocyanate or carboxylic acid). Thus, any of these materials are usefulin the preparation of the free-radically curable telechelic PEGoligomeric precursors.

In order for such chain extended precursors to maintain the desirablehydrophilicity and flexibility inherent in the PEG, it is important thatthe level of coupling agent be kept relatively low. Hence the molecularweight of the starting PEG should not be less than about 400 g/mole forthese chain extended precursors.

The telechelic oligomeric precursors useful in the present invention canbe prepared by reaction of the diol or diamine precursors describedabove with an electrophile having ethylenic unsaturation, (X in FormulaI above), and such other functionality that, upon reaction with the PEGdiol or diamine, not only an X group, but also an amide, substitutedamide, amine, urea, urethane, carbonate, ester, or ether moiety isprovided.

Nonlimiting examples of the types of functionality required in suchelectrophilic compounds include acid halide, acid anhydride, cyclicanhydride, and azlactones, each of which provides an amide moiety onreaction with the amine and an ester functionality on reaction with thealcohol; isocyanate, which provides a urea moiety on reaction with theamine and a urethane moiety on reaction with the alcohol; benzyl halide,which provides a substituted amine moiety on reaction with the amine andan ether moiety on reaction with the alcohol; and epoxy or acrylate,each of which provide a substituted amine moiety on reaction with theamine.

Nonlimiting examples of electrophiles suitable for reaction with the PEGdiol or diamine precursors to produce the telechelic oligomericprecursors of the present invention include but are not limited toisocyanatoethyl methacrylate; alkenyl azlactones such as vinyl dimethylazlactone and isopropenyl azlactone; m-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate; glycidyl methacrylate; acryloyl ethyl carbonicanhydride; maleic anhydride; methacrylic anhydride,; and multifunctionalacrylates such as hexanediol diacrylate and trimethylol propanetriacrylate. The alcohol can also be derivatized through anesterification reaction with, for example, acrylic acid, or through atransesterification reaction with, for example, an alkyl acrylate.Alternatively, the diol or diamine can be reacted first with a compoundcontaining two electrophilic groups, e.g. a diisocyanate, (or with acompound such as phosgene) and the resultant product reacted in a secondstep with a nucleophile, e.g., an amine or an alcohol, to provide theterminally difunctional oligomeric precursors. Nonlimiting examples ofsuch nucleophiles include hydroxyethyl acrylate, hydroxyethylmethacrylate, and hydroxypropyl methacrylate. Such an approach is alsouseful when an excess of coupling agent is used to prepare the chainextended PEG as described above.

The resulting telechelic oligomeric precursor can be represented byFormula I identified above. Preferably, R is represented by Formula IIbelow: ##STR1## wherein Z is selected from the group consisting of --O--and --NH-- and R"' is a divalent C₁ to C₄ alkyl radical.

Preferably, X comprises R'CH═C(R")--, wherein R' is selected from thegroup consisting of hydrogen and --COOH and R" is selected from thegroup consisting of hydrogen, methyl, and --CH₂ COOH. Most preferably,R' comprises hydrogen and R" is selected from the group consisting ofhydrogen and methyl.

The organic divalent linking group Y is generated upon reaction of theelectrophile with the diamine or diol and is chosen so as to activatethe ethylenically unsaturated monovalent X group towards free radicalpolymerization. The Y group accomplishes this by changing the electrondensity of X. Preferably, Y is selected from the group of structurescontaining aromatic moieties which, when bound to X, yield vinylpyridinyl or styrenic-type functionalities; structures containingcarboxyl moieties which when bound to X at the oxygen side yield vinylester or isopropenyl ester-type functionalities; structures containingcarboxyl moieties which when bound to X at the carbonyl side yieldacrylate, methacrylate, maleate, fumarate, and itaconate-typefunctionalities; structures containing carboxamide moieties which whenbound to X at the nitrogen side yield N-vinyl amide and N-isopropenylamide-type functionality; and structures containing carboxamide moietieswhich when bound to X at the carbonyl side yield acrylamide,methacrylamide, and maleimide-type functionalities.

The amount of oligomeric precursor of Formula I preferably ranges fromabout 4 to 60 weight percent (and most preferably about 15 to 25 weightpercent) of the hydrophilic pressure sensitive adhesive.

The essentially, non-volatile, polar plasticizer is present in an amountpreferably ranging from about 96 to 40 (and most preferably ranging fromabout 85 to 75) weight percent prior to in situ polymerization.

The plasticizer serves to minimize the crystallization of the PEG moietyof the polymeric network at ambient and mammalian body temperatures,increase the compliance of the polymeric network to give pressuresensitive adhesive properties and conformability to mammalian bodies andother curved surfaces, and modify the tack or thumb appeal of thepressure sensitive adhesive.

The plasticizer can also serve as a solvent to dissolve other additivesincluding initiators, electrolytes, and pharmacologically activecomponents.

The plasticizer is essentially non-volatile because using water alone asthe plasticizer for the oligomeric precursor of Formula I above yieldsmaterials with poor to moderate tack which are prone to rapid loss ofmoisture and a concomitant change into a leathery material when exposedto ambient conditions. Hence, preferred essentially non-volatile, polarplasticizers are hydroxy-containing plasticizers miscible with bothwater and the precursor, including those selected from the groupconsisting of alcohols, mixtures of alcohols, and mixtures of water andalcohols such that the mixture of alcohol, water, and oligomericprecursor is liquid in the uncured state and displays pressure sensitivetack once polymerized in situ. Preferably, the alcohol should have lowvolatility to minimize dryout problems and should not greatly interferewith the subsequent polymerization of the oligomeric precursor.

Nonlimiting examples of suitable alcohols include glycerin, propyleneglycol, dipropylene glycol, sorbitol, 1,3-butanediol, 1,4-butanediol,trimethylol propane, and ethylene glycol and derivatives given byFormula III:

    MO(CH.sub.2 CH.sub.2 O).sub.m H                            III

wherein

M is selected from the group consisting of hydrogen and C₁ through C₆alkyl,

and m is an integer of about 1 to about 25.

Most preferably, the essentially non-volatile, polar plasticizer is amixture of water and 300 or 400 molecular weight (weight average)polyethylene glycol. In Formula III, that molecular weight range issatisfied when m=7 or 9, respectively, and M=H. The selection of thisplasticizer mixture has been found to provide the best balance ofpressure sensitive adhesive properties.

In situ, solventless polymerization of the oligomeric precursor in thepresence of the plasticizer is accomplished by exposing it to a sourceof free radicals. As one skilled in the art will recognize, freeradicals may be generated by thermal, redox, or photochemical means orby exposure of the material to a source of actinic radiation.

Suitable thermal initiators include azo compounds, peroxides, andpersulfates and when the latter two groups are used in combination witha reducing agent such ascorbic acid or a bisulfite compound andoptionally, a catalytic amount of a transition metal salt such as ironor copper, redox generation of radicals may occur even at sub-ambienttemperatures.

When visible or ultraviolet light is used for curing, a photoinitiatoris included. Suitable photoinitiators include benzoin ethers,benzophenone and derivatives thereof, acyl phosphine oxides,acetophenone derivatives, camphorquinone, and the like. Suitable lightsources to effect this cure include medium pressure mercury lamps andlow intensity "black light" fluorescent bulbs. Initiator is generallyused at a concentration of from about 0.05% to about 5%.

In the absence of initiator, exposure to actinic radiation such aselectron beam irradiation or a cobalt 60 gamma source will also generatefree radicals.

Additives can also be incorporated into the mixture for alteringproperties of the resulting hydrophilic pressure sensitive adhesive.Nonlimiting examples include low levels of copolymerizable vinylmonomers and non-functionalized compatible polymers.

Low levels of copolymerizable vinyl monomers, particularly thosemiscible in the oligomeric precursor/plasticizer mixture, can serve toaccelerate the rate of polymerization, particularly when thefunctionalized PEG moiety in Formula I is capped with a relativelysluggish end-group such as the alpha-methyl styryl moiety obtained fromm-isopropenyl-alpha, alpha-dimethyl benzyl isocyanate. Preferredcopolymerizable monomers include acrylic acid and methacrylic acid andtheir ammonium and alkali metal salts, N-vinyl pyrrolidone, acrylamide,2-acrylamido-2-methyl propane sulfonic acid and its ammonium and alkalimetal salts, hydroxylethyl acrylate, hydroxyethyl methacrylate,2-ethoxyethyl acrylate, 2-ethoxyethyl methacrylate, and2-(2-ethoxyethoxy)ethyl acrylate.

When utilized, the amount of copolymerizable vinyl monomer preferablycomprises from about 2 to about 15 weight percent of the total weight ofresulting pressure sensitive adhesive.

Addition of non-functionalized compatible polymers can enhance theviscosity of the oligomeric precursor prior to polymerization to impartbetter coatability for, for example, pattern coating of the resultinghydrophilic pressure sensitive adhesive. Suitable polymers include thosethat are hydrophilic and compatible in the precursor/plasticizer mixtureincluding moderate and high molecular weight poly(ethylene oxide),poly(acrylic acid), poly(N-vinyl pyrrolidone), poly(vinyl alcohol), andpoly(acrylamide).

The precursor/plasticizer mixture can be coated via any of a variety ofconventional coating methods, such as roll coating, knife coating, orcurtain coating, or can be extruded. The low viscosity of the mixtureallows for injection into cavities of, for example, a monitoringbiomedical electrode for electrocardiography (ECG), or pattern coatingof the adhesive precursor is possible, particularly with viscosityenhancement. The mixture can be coated directly on to the flexiblesubstrate of choice prior to in situ polymerization, including metalfoils and metallized polymeric films for conductive adhesives, or can becoated and cured on a release liner to yield a transfer adhesive. Inthis latter application, it is desirable to embed a tissue paper ornon-woven fabric scrim in the precursor to allow for ease of handling.

Polymerizing is best accomplished with the exclusion of oxygen, eitherin an inert atmosphere such as nitrogen or argon, or by covering theprecursor with a non-oxygen permeable film. When done photochemically,this film cover should be substantially transparent to the wavelengthsof interest.

USEFULNESS OF THE INVENTION

The hydrophilic PEO pressure sensitive adhesives of the presentinvention are useful in a variety of applications including use as highmoisture vapor transmissive wound or burn dressings, as adhesives usedin transdermal drug delivery, as repulpable adhesives in, for example,splicing applications in the paper industry, and as conductive adhesivesor gels in biomedical electrode applications. In this last application,a high degree of pressure sensitive adhesive tack may not be requiredwhen, for instance, a non-conductive, hypoallergenic pressure sensitiveadhesive borders the conductive adhesive in the electrode construction.

The adhesives prepared according to the present invention possesssufficient cohesive strength to achieve generally more cohesion thanadhesiveness in use allowing for clean removal from skin. However, suchadhesives do not have internal integrity required for applications suchas hydrophilic contact lenses or membranes which must withstand largepressure differentials. When used as adhesive sheets, it may bedesirable to cure them with an embedded support to allow for ease inhandling and dimensional stability.

BIOCOMPATIBLE AND/OR THERAPEUTIC AND/OR IONICALLY-CONDUCTIVE ADDITIVES

Depending upon the use of the hydrophilic, PEO pressure sensitiveadhesive of the present invention, various biocompatible and/ortherapeutic and/or ionically-conductive materials can be included in theadhesive.

For example, adhesives of the present invention can be used asconductive adhesive in a biomedical electrode with the addition of anionically-conductive electrolyte to the adhesive. Nonlimiting examplesof electrolyte include ionic salts dissolved in the adhesive to provideionic conductivity and can include magnesium acetate, magnesium sulfate,sodium acetate, sodium chloride, lithium chloride, lithium perchlorate,sodium citrate, and preferably potassium chloride to enhance ionicconductivity of the hydrophilic pressure sensitive adhesive.

Alternatively, a redox couple such as a mixture of ferric and ferroussalts such as sulfates and gluconates can be added.

The amounts of these ionic salts present in adhesives of the presentinvention are relatively small, from about 0.5 to 7 percent by weight ofthe adhesive, and preferably about 2 to 5 weight percent. When a redoxcouple is used, the biomedical electrode can recover from an overloadpotential. U.S. Pat. No. 4,846,185 (Carim) discloses a redox coupletotalling not more than about 20 percent by weight of the adhesive.

Hydrophilic, PEO pressure sensitive adhesives of the present inventioncan also be used in the delivery of pharmaceuticals to or throughmammalian skin, such as topical or transdermal drug delivery systems.The pharmaceutical or other active ingredient can be compounded with theadhesive after polymerization, minimizing any possible deleteriousinteraction of the pharmaceutical or active ingredient with thepolymerizing process.

A type of therapeutic procedure both involving application of electricalcurrent to skin of a patient and a pharmaceutical is iontophoresis,which delivers an iontophoretically active pharmaceutical to or throughmammalian skin with aid of an electrical current.

The hydrophilic, PEO pressure sensitive adhesive can also be used intherapeutic mammalian skin coverings, such as dressings, wound closurematerials, tapes, and the like. Preferably, for mammalian skin coveringuses, other biologically active materials can be added to the adhesiveof the present invention after polymerization without deleteriouslyaffecting the biologically active material. Nonlimiting examples of suchother biologically active materials include broad spectrum antimicrobialagents where it is desired to reduce bacteria levels to minimizeinfection risk or treat the effects of infections at the skin or skinopenings of a mammalian patient. Broad spectrum antimicrobial agents aredisclosed in U.S. Pat. No. 4,310,509, which disclosure is incorporatedby reference. Nonlimiting examples of other antimicrobial agents includeparachlorometaxylenol; triclosan; chlorhexidine and its salts such aschlorhexidine acetate and chlorhexidine gluconate; iodine; iodophors;poly-N-vinyl pyrrolidone-iodophors; silver oxide, silver and its salts,antibiotics (e.g., neomycin, bacitracin, and polymyxin B). Antimicrobialagents can be included in the adhesive after polymerization in a weightfrom about 0.01 percent to about 10 percent by weight of the totaladhesive.

Other biocompatible and/or therapeutic materials can be added to theadhesive such as compounds to buffer the pH of the adhesive to provide anon-irritating pH for use with sensitive mammalian skin tissue or tootherwise maximize antimicrobial activity. Also, penetration enhancingagents or excipients can be added to the adhesive when thepharmaceutical or other active agent for topical or transdermal deliveryso requires.

BIOMEDICAL ELECTRODES

Biomedical electrodes employing hydrophilic, pressure sensitiveadhesives of the present invention having electrolyte contained thereinare useful for diagnostic and therapeutic purposes. In its most basicform, a biomedical electrode comprises a conductive medium contactingmammalian skin and a means for electrical communication interactingbetween the conductive medium and electrical diagnostic, therapeutic, orelectrosurgical equipment.

FIGS. 1 and 2 show either a disposable diagnostic electrocardiogram(ECG) or a transcutaneous electrical nerve stimulation (TENS) electrode10 on a release liner 12. Electrode 10 includes a field 14 of abiocompatible and adhesive conductive medium for contacting mammalianskin of a patient upon removal of protective release liner 12. Electrode10 includes means for electrical communication 16 comprising a conductormember having a conductive interface portion 18 contacting field 14 ofconductive medium and a tab portion 20 extending beyond field 14 ofconductive medium for mechanical and electrical contact with electricalinstrumentation (not shown). Means 16 for electrical communicationincludes a conductive layer 26 coated on at least the side 22 contactingfield 14 of conductive medium.

It is foreseen that a typical ECG conductor member 16 will comprise astrip of material having a thickness of about 0.05-0.2 millimeters, suchas polyester film and have a coating 26 on side 22 of silver/silverchloride of about 2.5-12 micrometers, and preferably about 5 micrometersthick thereon. Presently preferred is a polyester film commerciallyavailable as "Mellinex" 505-300, 329, or 339 film from ICI Americas ofHopewell, Va. coated with a silver/silver chloride ink commerciallyavailable as "R-300" ink from Ercon, Inc. of Waltham, Mass. A TENSconductor member 16 can be made of a nonwoven web, such as a web ofpolyester/cellulose fibers commercially available as "Manniweb" web fromLydall, Inc. of Troy, N.Y. and have a carbon ink layer 26 commerciallyavailable as "SS24363" ink from Acheson Colloids Company of Port Huron,Mich. on side 22 thereof. To enhance mechanical contact between anelectrode clip (not shown) and conductor member 16, an adhesively-backedpolyethylene tape can be applied to tab portion 20 on side 24 oppositeside 22 having the conductive coating 26. A surgical tape commerciallyavailable from 3M Company as "Blenderm" tape can be employed for thispurpose.

Non-limiting examples of biomedical electrodes which can usehydrophilic, pressure sensitive adhesives of the present invention asconductive adhesive fields include electrodes disclosed in U.S. Pat.Nos. 4,527,087; 4,539,996; 4,554,924; 4,848,353 (all Engel); 4,846,185(Carim); 4,771,713 (Roberts); 4,715,382 (Strand); 5,012,810 (Strand etal.); 5,133,356 (Bryan et al.) and copending and co-assigned U.S. patentapplication Ser. No. 07/686,049, the disclosures of which areincorporated by reference herein.

Because hydrophilic pressure sensitive adhesives of the presentinvention can also be characterized as gels having pressure sensitiveadhesive properties, the adhesives can also be used as the gelledcontact in a conventional gel electrolyte biomedical electrode having asnap-eyelet means of electrical communication. Further description ofsuch biomedical electrodes are found in U.S. Pat. Nos. 3,805,769(Sessions); 3,845,757 (Weyer); and 4,640,289 (Craighead), thedisclosures of which are incorporated by reference.

Nonlimiting examples of such biomedical electrodes are those marketed bya number of companies (including Minnesota Mining and ManufacturingCompany which markets using the brand "Red Dot"), including thosesnap-type monitoring electrodes typified by the exploded view of anelectrode 50 shown in FIG. 5.

A metallic stud 51, (such as stainless steel eyelet No. 304 commerciallyavailable from companies such as Eyelets for Industry of Thomaston,Conn.) joins a plastic, metallic plated eyelet 52 (such as an ABSplastic eyelet silver-plated and chlorided commercially available fromMicron Products of Fitchburg, Mass.) through an aperture in a polymericbacking 53 (such as front label stock of printed white polyethylenecommercially available from Prime Graphics of West Chicago, Ill.). Theinner surface of the polymeric backing is coated with an adhesive (suchas a phenolic-cured smoke crepe natural rubber based adhesive).Contacting the eyelet 52 at the plated surface is a wood pulp scrim 54(such as an "Airtex 399" scrim commercially available from James RiverCorporation of Green Bay, Wis.), loaded with a quantity 55 ofhydrophilic pressure sensitive adhesive of the present invention. Scrim54 and adhesive 55 reside in a cavity of a 0.16 cm thick polyethylenefoam 56 coated with either 12 grains of a 91:9 isooctylacrylate:N-vinyl-2-pyrrolidone copolymer pressure sensitive adhesive or18 grains of a 94:6 isooctyl acrylate:acrylic acid copolymer tackifiedwith a "Foral" branded colophony acid rosin, such as "Foral AX" or"Foral 85" rosins commercially available from Hercules Corporationpresent in an amount of about 35-40 weight percent of the copolymersolids. The pressure sensitive adhesive is covered by a tabbedantifungal liner 57 (such as 83 pound bleached release paper under thebrand "Polyslik S-8004" treated with "Calgon TK-100" brand fungicide,both liner and treatment commercially available from H.P. Smith Companyof Chicago, Ill.). Scrim 54 and adhesive 55 are protected by a cap 58,(such as a 0.25 mm "PETG" polyester film commercially available fromWeiss Company of Chicago, Ill.) secured in place by dual strips 59 ofadhesive tape (such as "3M" brand "Type 2185" tape). Biomedicalelectrodes marketed by a number of companies, and the components used insuch electrodes, provide combinations of alternative materials useful assnap-type monitoring biomedical electrodes to incorporate hydrophilicpressure sensitive adhesive of the present invention. The removal ofconductive gel and its supporting structure from the center of acommercially available monitoring biomedical electrode and thereplacement with hydrophilic pressure sensitive adhesive of the presentinvention can provide a superior biomedical electrode. Alternatively,such electrodes can be manufactured using equipment described in U.S.Pat. No. 4,640,289 (Craighead).

In some instances, the means for electrical communication can be anelectrically conductive tab extending from the periphery of thebiomedical electrodes such as that seen in U.S. Pat. No. 4,848,353 orcan be a conductor member extending through a slit or seam in aninsulating backing member, such as that seen in U.S. Pat. No. 5,012,810.Otherwise, the means for electrical communication can be an eyelet orother snap-type connector such as that disclosed in U.S. Pat. Nos.4,640,289 and 4,846,185. Further, the means for electrical communicationcan be a lead wire such as that seen in U.S. Pat. No. 4,771,783.Regardless of the type of means for electrical communication employed, ahydrophilic, pressure sensitive adhesive of the present invention,containing an electrolyte, can reside as a field of conductive adhesiveon a biomedical electrode for diagnostic, therapeutic, orelectrosurgical purposes.

MEDICAL SKIN COVERINGS

Medical skin coverings employing hydrophilic, PEO pressure sensitiveadhesives of the present invention, optionally having antimicrobial andother biologically active agents contained therein, are useful fortreatment of mammalian skin or mammalian skin openings, preferablyagainst the possibility of infection.

FIG. 3 shows a sectional view of a medical skin covering 30 having abacking material 32, a layer 34 of pressure sensitive adhesive of thepresent invention coated on backing material 32, and protected until useby a release liner 36. Preferably, antimicrobial 38 is contained inlayer 34 by adding agent 38 to the adhesive prior to coating on backingmaterial 32.

For use, the release liner 36 is removed and the layer 34 of pressuresensitive adhesive can be applied to the skin of the patient as a partof a medical tape, a wound dressing, a bandage of general medicinalutility, or other medical device having water moisture absorbingproperties.

The adhesive layer 34 may be coated on a layer of backing material 32selected from any of several backing materials having a high moisturevapor transmission rate for use as medical tapes, dressings, bandages,and the like. Suitable backing materials include those disclosed in U.S.Pat. Nos. 3,645,835 and 4,595,001, the disclosures of which areincorporated by reference. Other examples of a variety of filmscommercially available as extrudable polymers include "Hytrel^(R) 4056"and "Hytrel^(R) 3548" branded polyester elastomers available from E.I.DuPont de Nemours and Company of Wilmington, Del., "Estane" brandedpolyurethanes available from B.F. Goodrich of Cleveland, Ohio or"Q-thane" branded polyurethanes available from K.J. Quinn & Co. ofMalden, Mass.

The layer 34 of adhesive combined with a layer 32 of suitable backingmaterial can be used as a dressing.

Hydrophilic, PEO pressure sensitive adhesives of the present inventioncan be used as discrete gel particles dispersed in a continuous pressuresensitive adhesive matrix to form a two phase composite useful inmedical applications, as described in co-pending, co-assigned U.S.patent application Ser. No. 07/905,490, the disclosure of which isincorporated by reference herein.

The adhesive layer 34 can be coated on the backing layer 32 by a varietyof processes, including, direct coating, lamination, and hot lamination.The release liner 36 can thereafter be applied using direct coating,lamination, and hot lamination.

The methods of lamination and hot lamination involve the application ofpressure, or heat and pressure, respectively, on the layer of adhesivelayer 34 to the backing material layer 32. The temperature for hotlamination ranges from about 50° C. to about 250° C., and the pressuresapplied to both lamination and hot lamination range from 0.1 Kg/cm² toabout 50 Kg/cm².

PHARMACEUTICAL DELIVERY DEVICES

Pharmaceutical delivery devices employing hydrophilic, pressuresensitive adhesives of the present invention, optionally having atopical, transdermal, or iontophoretic therapeutic agent and excipients,solvents, or penetration enhancing agents contained therein, are usefulfor delivery of pharmaceuticals or other active agents to or throughmammalian skin.

FIG. 4 shows a sectional view of a transdermal or topical drug deliverydevice 40 having a backing layer 42, a layer 44 containing hydrophilic,PEO pressure sensitive adhesive of the present invention coated thereonand protected by a release liner 46. Other layers can be present betweenlayer 42 and layer 44 to house pharmaceuticals or other therapeuticagents. Otherwise, as shown in FIG. 4, pharmaceutical and other agents48 are dispersed in adhesive layer 44.

The backing layer 42 can be any backing material known to those skilledin the art and useful for drug delivery devices. Non-limiting examplesof such backing materials are polyethylene, ethylene-vinyl acetatecopolymer, polyethylene-aluminum-polyethylene composites, and"ScotchPak™" brand backings commercially available from Minnesota Miningand Manufacturing Company of St. Paul, Minn. (3M).

The release liner 46 can be any release liner material known to thoseskilled in the art. Non-limiting examples of such release linerscommercially available include siliconized polyethylene terephthalatefilms commercially available from H.P. Smith Co. and fluoropolymercoated polyester films commercially available from 3M under the brand"ScotchPak™" release liners.

The therapeutic agent 48 can be any therapeutically active materialknown to those skilled in the art and approved for delivery topically toor transdermally or iontophoretically through the skin of a patient.Non-limiting examples of therapeutic agents useful in transdermaldelivery devices are any active drug or salts of those drugs, used intopical or transdermal applications, or growth factors for use inenhancing wound healing. Other therapeutic agents identified as drugs orpharmacologically active agents are disclosed in U.S. Pat. Nos.4,849,224 and 4,855,294, and PCT Patent Publication WO 89/07951.

Excipients or penetration enhancing agents are also known to thoseskilled in the art. Non-limiting examples of penetration enhancingagents include ethanol, methyl laurate, oleic acid, isopropyl myristate,and glycerol monolaurate. Other penetration enhancing agents known tothose skilled in the art are disclosed in U.S. Pat. Nos. 4,849,224; and4,855,294 and PCT Patent Publication WO 89/07951.

The method of manufacturing a transdermal delivery device depends on itsconstruction.

The drug delivery device 40 shown in FIG. 4 can be prepared using thefollowing general method. A solution is prepared by dissolving thetherapeutic agent 48 and such optional excipients as are desired in asuitable solvent and mixed into either plasticizer prior to forming theadhesive, during the formation of the adhesive, or directly into thealready formed adhesive. The resulting loaded adhesive is coated on thebacking layer 42. A release liner 46 is applied to cover loaded adhesivelayer 44.

EXAMPLES

The invention is further illustrated by the following examples, in whichall parts are by weight unless otherwise stated.

Initial Tack

The adhesive composition was evaluated for initial tack immediatelyfollowing curing. In this test, firm pressure was applied to the samplewith a thumb and the thumb removed. Tack was qualitatively assessed andassigned a value of 1 through 5 where 1=very firm, tack free;2=moderately firm, acceptable tack; 3=moderately soft, good tack, noresidue; 4=moderately soft, acceptable tack, no residue; 5=very soft,residue transferred to thumb on removal. On this scale values of 2, 3,and 4 represented adhesives with a desirable balance of sufficientcompliance to possess tack and sufficient integrity to possess cohesivestrength.

EXAMPLES 1-5 AND COMPARATIVE EXAMPLES A AND B

2,000 mw poly(ethylene oxide) diamine (available from Texaco ChemicalCompany, Houston, Tex. under the brand "Jeffamine ED-2001") was meltedby holding in a 55° C. oven for 4 hours. 350 grams was dissolved in amixture of 130.2 g deionized water and 130.2 g 300 mw polyethyleneglycol, PEG 300, (available from BASF Corporation, Parsippany, N.J.under the brand "Pluracol E300") and allowed to cool to roomtemperature. 87.2 gram aliquots (containing 50 g or 50 milliequivalentsof the poly(ethylene oxide) diamine "Jeffamine ED-2001") of theresulting solution were charged into each of six 200 milliliter glassjars. These were placed in a water bath at room temperature and anoverhead mechanical stirring paddle immersed in the solution. Isophoronediisocyanate, IPDI, (available from Aldrich Chemical Company, Milwaukee,Wis.) in the amounts shown in Table I was added portionwise over thecourse of several minutes, so as to maintain a temperature below 45° C.Stirring was continued until either 10 minutes had elapsed, or thesolution became too viscous to satisfactorily stir. The mixing paddlewas withdrawn, 2-vinyl-4,4-dimethyl-2-oxazolin-5-one, VDM, (availablefrom S.N.P.E., Princeton, N.J.) in the amounts shown in Table I wascharged in one portion, the mixture shaken or hand stirred asappropriate to obtain a homogeneous mixture, capped, and left in thedark overnight at room temperature. The approximate molecular weight ofthe resulting chain extended, functionalized, poly(ethylene glycol)oligomeric precursor is shown in Table I and was calculated based onfirst principles with the assumption that the diamine and diisocyanateare of high purity and that the reactions go to completion with no sidereactions. The percent solids of the 2,000 and 4,000 mw oligomericprecursors were adjusted slightly by addition of 0.8 g and 0.4 g,respectively, of a 1/1 mix of PEG 300 and water so that all of thesematerials were at 60% solids in a 1/1 PEG 300/water mixture. Portions ofeach were diluted to 30% solids (5 g of 60% plus 5 g of 1/1 PEG300/water) and 10% solids (4 g of 60% and 20 g of 1/1 PEG 300/water) and0.5% 2-hydroxy-2-methyl-1-phenyl-propan-1-one photoinitiator (availablefrom Ciba-Geigy Corporation, Hawthorne, N.Y. under the brand "Darocur1173") was charged to each. After mixing well, a portion of each wasdistributed between 1.5 mil (0.038 mm) 164Z siliconized polyester linersavailable from the HP Smith Division of James River Corporation to athickness of 25 mil (0.63 mm). The resulting laminate was exposed to abank of six Sylvania 15 watt F15T8 350 black light bulbs at a distanceof 15 cm for 10 minutes giving a total dose of 585 mJ/sq. cm. asmeasured by a Model UR365CH3 UV Integrating Radiometer available fromElectronic Instrumentation & Technology, Incorporated, Sterling, Va. Thetop liner was removed from the cured material and the tack assessed asdetailed above. Results are presented in Table I.

                                      TABLE I                                     __________________________________________________________________________                                         Tack on Cure                                 ED-2001   IPDI     VDM     Theoretical                                                                         10% 30% 60%                              Ex. g    m equiv                                                                            g   m equiv                                                                            g   m mole                                                                            MW    Solids                                                                            Solids                                                                            Solids                           __________________________________________________________________________    Comp                                                                              50   50   0   0    6.96                                                                              50  2,000 1   1   1                                1   50   50   2.78                                                                              25   3.48                                                                              25  4,000 2   1   1                                2   50   50   4.17                                                                              37.5 1.74                                                                              12.4                                                                              8,000 5   3   2                                3   50   50   4.63                                                                              41.6 1.16                                                                              8.3 12,000                                                                              5   5   3                                4   50   50   4.86                                                                              43.7 0.87                                                                              6.3 16,000                                                                              5   5   3                                Comp.                                                                             50   50   5.00                                                                              45.0 0.70                                                                              5.0 20,000                                                                              5   5   5                                B                                                                             5   1/1                              4                                            Mix of                                                                        2K & 20K                                                                  __________________________________________________________________________

The results in Table I show that in order to achieve a balance ofcohesion and tack, both oligomer molecular weight and percent solids areimportant and that molecular weights above about 2,000 and below about20,000 are useful as are percent solids in the 10 to 60% region.Although neither the 2,000 (comparative example A) or 20,000(comparative example B) molecular weight materials cure to give usefuladhesives in this percent solids region, a 1/1 blend of them does give auseful adhesive (example 5).

EXAMPLES 6-10

6,000 molecular weight poly(ethylene oxide) diamine (available fromTexaco Chemical Company, Houston, Tex. under the brand "JeffamineED-6000") was melted by holding in a 55° C. oven for 4 hours. 15 grams(5 milliequivalents) was charged to 100 milliliter jars containing 35grams of the plasticizers listed in Table II, mixed, and allowed to coolto room temperature. 0.70 g (5 mmole) VDM was charged to each, the jarcapped, the mixture shaken to obtain a homogeneous mixture, and left inthe dark overnight. To 6 g of Example 6 (30% solids VDM capped"Jeffamine ED-6000" poly(ethylene oxide) in PEG 200) was charged 0.03 g2-hydroxy-2-methyl-1-phenyl-propan-1-one photoinitiator ("Darocur 1173")and the resulting solution cured and evaluated as described above andgiven a tack value of 3. A 4 g portion of the 30% solids solutions ofExamples 7 through 10 were diluted further to 20% solids with 2 g of therespective plasticizers, 0.03 g of photoinitiator ("Darocur 1173")charged, and cured and evaluated as described above, also all givingtack values of 3. These examples thus illustrate that a variety ofplasticizers are useful for preparation of the adhesives described inthe present disclosure.

                  TABLE II                                                        ______________________________________                                                                            Tack                                      Example Plasticizer        Solids   Value                                     ______________________________________                                        6       200 mw Poly(ethylene                                                                             30%      3                                                 glycol).sup.a                                                         7       Dipropylene glycol.sup.b                                                                         20%      3                                         8       "Polyglycol P425".sup.c                                                                          20%      3                                         9       "Polyglycol 15-200".sup.d                                                                        20%      3                                         10      350 mw poly(ethylene glycol)                                                                     20%      3                                                 monomethyl ether.sup.e                                                ______________________________________                                         .sup.a Available from Sigma Chemical Company, St. Louis, MO                   .sup.b Available from Aldrich Chemical Company, Milwaukee, WI                 .sup.c Brand of 425 mw poly(propylene glycol) from Dow Chemical, Midland,     MI                                                                            .sup.d Brand of 2600 mw copolymer of EO and PO from Dow Chemical, Midland     MI                                                                            .sup.e Available from Union Carbide, Danbury, CT under the "Carbowax"         brand                                                                    

EXAMPLES 11 THROUGH 16

A 6,000 molecular weight difunctional acrylate terminated poly(ethyleneglycol) oligomer was prepared by dissolving 20 g (6.66 milliequivalents)6,000 mw PEG (available from Fluka Chemical Corporation, Ronkonkoma,N.Y.) in 20 g methylene chloride in a 100 milliliter round bottom flaskequipped with magnetic stirring bar, charging 1.01 g (10 millimoles)triethylamine (available from Aldrich Chemical Company, Milwaukee,Wis.), and with magnetic stirring while cooling in an ice water bathcharging 0.66 g (7.3 millimoles--10% excess) acryloyl chloride dropwise.After stirring for 30 minutes, the precipitated triethylaminehydrochloride salt was filtered off, the solution concentrated somewhaton a rotary evaporator, the solution refiltered and diluted with 20 gdeionized water. The resulting cloudy/inhomogeneous solution wasconcentrated further on the rotary evaporator, this time with mildheating until all methylene chloride was removed as indicated by thesolution becoming clear. Solids on this aqeuous solution were analyzed,finding 48%. 2 g aliquots (containing 1.0 g 6,000 mw diacrylated PEG)were diluted with 2 g of the plasticizers listed in Table III, 0.02 g ofphotoinitiator ("Darocur 1173") added, and the 25% solids homogeneoussolutions which resulted on mixing cured and evaluated for tack asdetailed above. Results are presented in Table III and demonstrate thatdifunctional PEG oligomers obtained from PEG diols are useful in thepractice of the present invention as are mixtures of a variety ofplasticizers and water.

                  TABLE III                                                       ______________________________________                                                                      Tack                                            Example   Plasticizer         Value                                           ______________________________________                                        11        Glycerine.sup.e     3                                               12        Propylene glycol.sup.f                                                                            4                                               13        1,4-butanediol.sup.g                                                                              4                                               14        350 mw poly(ethylene glycol)                                                                      3                                                         monomethylether.sup.h                                               15        1450 mw poly(ethylene glycol).sup.h                                                               3                                               16        "Butyl carbitol".sup.i                                                                            4                                               ______________________________________                                         .sup.e Available from Mallinkrodt, Inc. Paris, KY                             .sup.f Available from EM Industries, Gibbstown, NJ                            .sup.g Available from Aldrich Chemical Company, Milwaukee, WI                 .sup.h Available under the "Carbowax" brand from Union Carbide, Danbury,      CT                                                                            .sup.i Brand of the diethyleneglycol monobutylether available from Union      Carbide, Danbury, CT                                                     

EXAMPLES 17 THROUGH 20

90 g of diamine ("Jeffamine ED-6000") was dissolved in 210 g of"Carbowax" PEG 350 monomethyl ether. To 50 g aliquots of the resultingsolution (containing 15 g diamine ("ED-6000") or 5 milliequivalents) wascharged 5 millimoles of the capping agents detailed below. After mixingto homogeneity, 2the resulting solutions were left in the dark at roomtemperature overnight.

Example 17: 0.70 g 2-vinyl-4,4-dimethyl-2-oxazolin-5-one, VDM, charged.2 g of the resulting 30% solids solution was diluted with 4 g "Carbowax"PEG 350 monomethyl ether and 0.03 g "Darocur 1173" charged. Curing andtack evaluation on this 10% solids solution gave a tack value of 4.

Example 18: 0.78 g isocyanatoethyl methacrylate, (available from ShowaRhodia Chemicals K.K., Tokyo, Japan) charged. 2 g of the resulting 30%solids solution was diluted with 2 g "Carbowax" PEG 350 monomethyl etherand 0.02 g "Darocur 1173" added. Curing and tack evaluation on this 15%solids solution gave a tack value of 2.

Example 19: 1.01 g m-isopropenyl-alpha,alpha-dimethyl benzyl isocyanate(available from American Cyanamide, Wayne, N.J. under the brand "m-TMI")charged. 6 g of the resulting 30% solids solution was diluted with 2.55g "Carbowax" PEG 350 monomethyl ether and 0.45 g acrylic acid (availablefrom BASF Corporation, Parsippany, N.J.) and 0.03 g "Darocur 1173"added. Curing and tack evaluation on this 20% solids solution alsocontaining 5% acrylic acid gave a tack value of 2.

Example 20: 0.77 g methacrylic anhydride (available from AldrichChemical Company, Milwaukee, Wis.) charged. 6 g of the resulting 30%solids solution was diluted with 2.82 g "Carbowax" PEG 350 monomethylether and 0.18 g acrylic acid and 0.03 g "Darocur 1173" added. Curingand tack evaluation on this 20% solids solution also containing 2%acrylic acid gave a tack value of 2.

EXAMPLE 21

Into a 250 milliliter round bottomed 3-necked flask equipped withmechanical overhead stirrer and distillation head was charged 22.5 g10,000 mw poly(ethylene glycol), PEG 10K, (available from HoechstAktiengesellschaft, Frankfurt, Germany) and 22.5 g 8,000 mwpoly(ethylene glycol), PEG 8K, (available from Dow Chemical Company,Midland, Mich.). The flask was immersed in an oil bath at 85° C. and thePEG mixture melted. With stirring 180 milligrams of "Isonox 129" brandantioxidant (available from Schenectady Chemicals, Freeport, Tex.), 20 gmethyl acrylate (available from Hoechst Celanese Corporation, Dallas,Tex.), and 2.2 g p-toluene sulfonic acid monohydrate (available fromAldrich Chemical Company, Milwaukee, Wis.) was charged in that order.The reaction was continued for 4 hours in the 85° C. oil bath whileslowly bubbling dry air through the reaction mixture. A moderate vacuum(water aspirator, 20 torr) was then pulled on the flask for 30 minutesto remove excess methyl acrylate, then a high vacuum (vacuum pump, <1torr) pulled to remove the last traces. 45 milliliters of deionizedwater was charged to the warm fluid and the resulting solution cooled toroom temperature and transfered to a storage jar. Aqueous potassiumhydroxide was added to bring the pH to 7. Solids on this aqueoussolution were analyzed, finding 48%. 43.75 g of this (containing 21 g ofa 1/1 mix of acrylate functional PEG 8K and PEG 10K) was mixed with 0.25g deionized water, 16 g of a 25% aqueous solution of potassium chloride(available from Fisher Scientific, Fair Lawn, N.J.), and 30 g of 300 mwpoly(ethylene glycol) (available from BASF Corporation, Parsippany, N.J.under the brand "Pluracol E300"). To one 36 g portion of the resultingsolution was charged 4 g of a solution of 1.13 g 30% aqueous hydrogenperoxide (available from Aldrich Chemical Company, Milwaukee, Wis.) in48.9 g deionized water. To another 36 g portion of the resultingsolution was charged 4 g of a solution of 1.76 g ascorbic acid and 39milligrams ammonium iron (II) sulfate hexahydrate (both available fromAldrich) in 48.2 g deionized water. The two solutions were combined,mixed well, and poured between 1.5 mil (0.038 mm) 164Z siliconizedpolyester liners available from the HP Smith Division of James RiverCorporation to a thickness of 25 mil (0.63 mm). The resulting laminatecured on standing at room temperature within 30 minutes. The top linerwas removed from the cured material and the tack assessed as detailedabove, finding a value of 3. This example demonstrates the use of redoxchemistry to cure a mixture of acrylated PEG diols (21%) in a 45/30mixture of water and PEG 300 also containing 4% KCl.

EXAMPLE 22

Into a 500 milliliter 3-neck round bottomed flask equipped with nitrogeninlet and overhead mechanical stirrer was charged 60 g 8,000 mwpoly(ethylene glycol) (available from Dow Chemical, Midland, Mich.), 50g 12,000 mw poly(ethylene glycol) (available from HoechstAktiengesellschaft, Frankfurt, Germany), and 100 g chloroform. Afterstirring under nitrogen to dissolve the PEG mixture, 0.5 milliliters ofa 0.33M stannous octoate (available from ICN Pharmaceuticals, CosaMesta, Calif.) in toluene and 0.2 milliliters triethyl amine was added.5.6 g isophorone diisocyanate in 20 g chloroform was added in oneportion and stirring continued for 1 hour at room temperature. 3.3 g of2-hydroxyethyl methacrylate (available from Aldrich Chemical Company,Milwaukee, Wis.) was charged, rinsing in with 20 milliliters additionalchloroform. After stirring at room temperature for 18 hours, thechloroform was removed with a rotary evaporator at high vacuum and 75°C. The resulting oligomeric precursor was formulated into a hydrophilicpressure sensitive adhesive by mixing 4 parts with 50 parts deionizedwater, 4 parts potassium chloride, and 42 parts PEG 300. Portions werecured photochemically and assessed using the procedure described aboveafter charging 0.05% "Darocur 1173" photoinitiator. Thermalpolymerization was also conducted by adding to a portion 0.1%azo-bis(isobutyronitrile) (available from E.I. Dupont, Wilmington, Del.under the brand "Vazo 64"), sealing in a polyethylene bag, andsubmersing in a 80° C. water bath for 30 minutes. In each case theresulting adhesive had a tack value of 4.

EXAMPLES 23 AND 24

1440 g of oven-melted "Jeffamine ED-2001" was charged into a 4 literglass jar containing 536.7 g deionized water and 960 g of 400 mwpoly(ethylene glycol), PEG 400, (available from BASF Corporation,Parsippany, N.J. under the brand "Pluracol E400"). The mixture wasstirred with an overhead mechanical stirrer and cooled in a water bathwhile 120 g of isophorone diisocyanate was charged portionwise tomaintain the reaction temperature below 45° C. Residual IPDI was rinsedwith 80 g PEG 400 and stirring was continued for 2 hours. 50.1 g2-vinyl-4,4-dimethyl-2-oxazolin-5-one was charged in one portion,rinsing in with 33.4 g PEG 400. The mixture was stirred to homogeneity,capped and left in the dark for three days. 1600 g of this solution wastransferred to a second 4-liter jar and diluted with 419 g deionizedwater, 609.5 g PEG 400, and 609.5 g of a 25% aqueous solution ofpotassium chloride. A Brookfield viscosity on the resulting 21/4/30/30oligomer/KCl/PEG 400/water solution was taken, showing 265 centipoise. Asecond 1600 g portion of the capped oligomer solution was diluted insimilar fashion but further had 76.2 g of a 300,000 molecular weightpoly(ethylene oxide) (available from Union Carbide, Danbury, Conn. underthe brand "Polyox N-750") dissolved in it. This 21/4/30/30/2oligomer/KCl/PEG 400/water/PEO 300K solution had a Brookfield viscosityof 1300 centipoise. To 170 g of the low viscosity material or 174 g ofthe moderate viscosity material charged 10 g of 0.2M aqueous ascorbicacid, 10 g of 0.00067M ammonium iron (II) sulfate hexahydrate, and,after mixing well, 10 g of 0.2M hydrogen peroxide. The resultingsolutions were mixed well, cured between siliconized polyester liners,and evaluated as described in Example 21 above. Both adhesives had atack value of 3. These examples show that moderate levels of highmolecular weight polymer can be added to enhance viscosity withoutgreatly influencing cure or adhesive properties.

EXAMPLE 25

Into a 190 liter stainless steel reactor was vacuumed 6.1 kg deionizedwater, 12.2 kg PEG 300, and 18.2 kg "Jeffamine ED-2001" which had beenmelted by holding in an oven at 65° C. for 8 hours. Medium agitation wasstarted and the batch temperature was adjusted to 22° C. 1511 g of IPDIwas added incrementally so that the batch temperature did not exceed 32°C. The container which held the IPDI was then rinsed with 8.4 kg PEG300, flushing the lines into the kettle as well. The mixture was stirredfor 1 hour at 22° C., then 630 g 2-vinyl-4,4-dimethyl-2-oxazolin-5-one,VDM, was charged in one portion, rinsing with 8.4 kg additional PEG 300.After stirring for 2 hours at 22° C., a solution of 3.9 kg potassiumchloride in 22.9 kg deionized water was charged and mixing continued for30 minutes. The resulting oligomeric precursor was drained through a25-micrometer filter. To a 425 g portion of this precursor was added 25g deionized water and 50 g of a solution of 3.52 g ascorbic acid and78.4 milligrams ammonium iron (II) sulfate hexahydrate in 96.4 gdeionized water. To a second 425 g portion of the precursor was charged25 g deionized water and 50 g of a solution of 2.27 g 30% aqueoushydrogen peroxide in 97.7 g deionized water. These two solutions wereused to fill the adjacent chambers of an "Express" brand two partdelivery system (available from 3M Dental Products Division, St. Paul,Minn.) which had been modified to enable delivery through an 18 gaugesyringe needle. This modification was accomplished by removing themixing element from the static mixer and placing the cut-off end of adisposable syringe at the end of the static mixer, then replacing themixing element. In this fashion the syringe needle could by joined tothe static mixer. The two components were delivered through the staticmixer into the gel chamber of the electrode blanks shown in FIG. 5 andprepared using equipment such as that described in U.S. Pat. No.4,640,289 (in this case assembled with prechlorided silver/silverchloride eyelets 52) by inserting the needle through the front label 53of the blank diametrically opposite to a vent hole which had beenpunched in the cap 58 with a 26 gauge needle. In this way it waspossible to completely fill the cap. The resulting adhesive polymerizedin situ within 30 minutes giving a material with a tack value of 3.After conditioning these electrodes for 3 days at 50° C. electricaltesting was conducted as described below with results presented in TableIV.

EXAMPLE 26

Using the same procedure and scale described for Example 25, a secondbatch of precursor was prepared. The only difference was that the IPDIand VDM charges were changed slightly, using 1594 g IPDI and 530 g VDMresulting in a somewhat softer, more chain extended precursor. 2914 g ofthis precursor was diluted with 211.5 g PEG 300 and 831.5 g deionizedwater into which 22.9 g potassium chloride and 0.48 g sodium chlorite(available from Aldrich Chemical Company, Milwaukee, Wis.) had beendissolved. To this precursor was charged 20 g "Darocur 1173"photoinitiator. A 20 miililiter syringe was filled with this and an 18gauge needle attached. Injection was done into the electrode blanksshown in FIG. 5 and prepared using equipment such as that described inU.S. Pat. No. 4,640,289 (this time assembled with a silver plated eyelet52) on the cap 58 side that diametrically opposed the vent hole (punchedwith a 26 gauge needle). The resulting filled electrode was clamped to aboard and passed through a PPG Industries UV Processor two times at 10meters per minute with two medium pressure mercury lights on at a 80watts/cm (200 watts/inch) power setting. At this speed and power settingeach pass gave a dose of 61 mJ/sq. cm. as measured by the EIT UVIntegrating Radiometer described above. The resulting adhesive curedimmediately giving a material with a tack value of 3. After conditioningthese electrodes for 3 days at 50° C., electrical testing was conductedas described above with results presented in Table IV.

ELECTRICAL TESTING OF EXAMPLES 25 AND 26

The gel-filled blank electrode 50 depicted in FIG. 5 formed a testelectrode unit. Two electrode units, joined together adhesive surface toadhesive surface to form an electrode pair. This electrode pair was thentested in order to characterize its electrical response in comparison tothe American National Standard developed by the Association for theAdvancement of Medical Instrumentation for disposable ECG electrodes(approved 17 Dec. 1991 by the American National Standards Institute).The guideline values specified by this standard for such electrode pairsare:

a) DC offset voltage <100 mV

b) AC impedance at 10 Hz <3000 ohms

c) Defibrillation recovery--rate of change of residual polarizationpotential <+/- 1 mV/second and 10 Hz impedance <3000 ohms at the end offour test discharges

d) Internal noise <150 mV

e) Bias current tolerance <100 mV over a period of at least eight hours

An Xtratek Electrode Tester (available from Xtratek, Lenexa, Kans.) wasused to conduct these characterizations. Values obtained for an averageof 16 pairs of electrodes of Examples 25 and 26 are shown in Table IV,except for noise and bias where values are only from a single pair ofelectrodes of Examples 25 and 26.

                  TABLE IV                                                        ______________________________________                                                       Defibrillation                                                        AC      Recovery                                                       Ex-  DC      Impedance       ohms                                             am-  Offset  at 10 Hz  change                                                                              impedance                                                                             Noise Bias                               ple  (mV)    (ohms)    mv/sec                                                                              at 10 Hz                                                                              (mV)  (mV)                               ______________________________________                                        25   1.76    154.0     <±1                                                                              11.2    0.0   5.3                                26   0.19    176.4     <±1                                                                              9.4     0.0   3.3                                ______________________________________                                    

Without being limited to the foregoing, the invention is hereby claimed.

What is claimed is:
 1. A method of preparing a hydrophilic, pressure sensitive adhesive comprising subjecting a mixture of a difunctional poly(ethylene glycol) oligomeric precursor and an essentially non-volatile polar plasticizer to a source of free radicals to induce free radical polymerization of the oligomeric precursor in the presence of plasticizer to form a hydrophilic poly(ethylene oxide) pressure sensitive adhesive.
 2. The method according to claim 1, wherein the subjecting step comprises:(a) mixing the oligomeric precursor and the plasticizer and a free radical initiator into a mixture; (b) coating the mixture on a substrate; and (c) free radically polymerizing the oligomeric precursor in the presence of the plasticizer in situ on the substrate.
 3. The method according to claim 2, further comprising optionally mixing an electrolyte, an antimicrobial agent, or a pharmaceutical into the adhesive. 